Cultured mammalian cells and plant seedling systems will be used to evaluate fundamental and practical aspects of the treatment of cancer with densely ionizing radiations. These well tried systems have been used widely in the past to determine values for the oxygen enhancement ratio (OER) and the relative biological effectiveness (RBE) of high energy cyclotron produced neutrons currently used for radiotherapy. It is proposed to extend their use to measurements involving negative-pi-mesons at Los Alamos, and heavy ions at the BEVALAC. For neutrons, RBE is known to be a strong function of dose. In all probability it will also depend on the phase of cell cycle, being higher for cells in S, and lower for mitotic cells and cells at the border between G1 and S. The complex inter-relationship between, on the one hand, RBE and dose, and on the other hand RBE and cell age, will be studied in detail for one source of high energy cyclotron-produced neutrons. The need to do so is based on the empirical observation that RBE's determined with in vivo normal tissue systems, even at a given dose level, vary significantly from one biological system to another; it is our thesis that this variation is a result, principally, of different mixes of cell ages in the various populations at risk. Lastly, the new generation of drugs (the nitroimidazoles) which selectively sensitize hypoxic cells, will be tested with both gamma-rays, and cyclotron-produced neutrons. High LET radiations and hypoxic sensitizers represent two of the most promising and exciting new directions in radiotherapy.